Potential Application of the Staphylococcus aureus DNA Mimic Protein Saugi in Combating Human Viral Disease

DNA mimic proteins act as control factors by preventing DNA-binding proteins from binding to their target DNA. They have been found in virus, bacteria and eukaryotes, and are involved in many important control mechanisms. To date, however, despite their importance to living cells, only a handful of DNA mimics (less than 20) have been reported. In our previous studies, we identified five new DNA mimic proteins: white spot syndrome virus ICP11, bacteriophage T4 Arn, Neisseria DMP19, Neisseria DMP12 and Staphylococcus SAUGI. In the study proposed here, we now aim to explore the therapeutic potential of SAUGI in combating human viral disease. Functionally, SAUGI targets the Staphylococcus aureus DNA repair enzyme uracil DNA glycosylase (SAUDG). However, since the protein structure of SAUDG is extremely similar to that of the UDGs encoded by several human pathogenic viruses, including Vaccinia virus, Herpes simplex virus and Epstein-Barr virus, it is very likely that SAUGI will also interact with these viral UDGs. We therefore intend to use structural and proteomic approaches to analyze the interactions between SAUGI and the UDGs of these viruses. Further, since these viral UDGs play important roles in viral replication, we will also use viral recombination experiments to study the effect of SAUGI on virus replication. We anticipate that the results of this work will greatly extend our understanding of DNA mimics as well as potentially open the way for novel applications for this kind of protein.